Urine is an easily accessed specimen that has not been well exploited for cancer biomarker studies. We have developed a new stable isotope mass tag (13C Phenylisocyanate, PIC) that has several advantages for protein quantification in complex mixtures. We describe a complete analytic platform for urine biomarker discovery using PIC labeling. This platform includes: 1) custom designed software (PICquant) to automatically quantify labeled peaks, 2) a spectrum-comparison algorithm that groups spectra into a Registry of spectra representing unique peptide families, and 3) enhanced peptide sequencing by distinguishing b- and y-ion series in CID spectra. Completing the platform is a clinical registry that links acquired specimens to current and prospective clinical information including outcomes, and that enables multivariate clustering of disease states with quantified protein families. The mature PICquant platform will provide nearly completely automated data analysis, allowing assembly of numerous patient samples into complete protein abundance profiles akin to gene expression array data. Additionally, the expanding Registry database will be of use to other investigators processing either PIC-labeled or unlabeled peptide spectra.